Effect of chronic administration of clonidine, propranolol and alpha-methyldopa on extensibility and biochemical properties of the veins in renal and spontaneous hypertension
Greenberg, S.
Journal of Pharmacology and Experimental Therapeutics 218(3): 779-790
1981
ISSN/ISBN: 0022-3565 PMID: 7264961 Document Number: 169916
Four mo. old Wistar-Kyoto rats (WKY), subjected to 1-kidney, 1-clip Goldblatt hypertension (1-KGH) or unilateral nephrectomy (WKY-NEPHREX) and age-matched WKY and spontaneously hypertensive rats (SHR) were evaluated for the functional and biochemical properties of their portal and femoral veins. Portal and femoral veins obtained from SHR and 1-KGH, when compared with veins obtained from WKY and WKY-NEPHREX, were less extensible, contained more protein, exhibited a greater uptake of [2-14C]lysine, [2-14C]glucosamine, [7-3H]fucose, a normal rate of uptake of [2-14C]thymidine and an increased content of endogenous DNA. These differences were most pronounced in SHR and less marked in 1-KGH. Venous pressures were not elevated in SHR or 1-KGH, when compared with venous pressures of the corresponding normotensive WKY or WKY-NEPHREX. Clonidine (0.075-0.3 mg/kg per day), .alpha.-methyldopa (25 and 100 mg/kg per day) and propranolol (1.5 and 6.0 mg/kg per day) increased the extensibility of portal and femoral veins obtained from both SHR and 1-KGH. Clonidine produced dose-related decreases in the uptake of radiolabeled glucosamine, fucose and lysine, precursors of cellular glycoproteins and proteins and total vein protein in the blood vessels of SHR and 1-KGH. These effects were minimal on the veins of WKY and WKY-NEPHREX and were not inhibited by phentolamine. The effects of .alpha.-methyldopa and propranolol were similar to, but less pronounced than, those of clonidine. Aberrant venous function is not a genetically linked defect specific for the SHR, but is present in experimental Goldblatt hypertension. The severity of the changes appear to be related to the severity of the hypertension. The extensibility changes appear to be related to the altered protein synthesis exhibited by the veins from SHR and 1-KGH. The ability of clonidine, propranolol and .alpha.-methyldopa to reverse the extensibility changes in the veins appears to be related to their effects on protein and glycoprotein synthesis, rather than by a reduction in intravascular pressure, withdrawal of sympathetic tone to the veins or by stimulation of vascular smooth muscle .alpha. receptors. Alternatively, these drugs may act to inhibit the release and/or synthesis of a trophic or circulating humoral factor(s) responsible for the abnormalities in venous smooth muscle.